David biweekly meeting
Mechanical role of Type I myosin in CME theory project
recent progress
- systematically discussed model parameters with Matt and Ross to classify each
into categories:
- fixed in "baseline" model
- myosin diffusion rate
- myosin step size force sensitivity (slip-through has not been detected experimentally)
- varied for focus of modeling "experiments"
- unloaded myosin-actin unbinding rate
- force sensitivity of myosin-actin unbinding rate
- resistance to bud internalization
- myosin copy number
- fixed for now, but flagged to revisit in future investigations
- myosin-actin binding rate (set by phosphate release rate in ATPase cycle)
- myosin-membrane binding kinetics and force sensitivity
- direction-dependent force sensitivity of actin-myosin unbinding
- fixed in "baseline" model
- decided on sticking with the older version of cytosim for this project because I don't know how long it will take to make the type I myosin in Matt's new version
- successfully implemented diffusion of myosins model (I used to have them
fixed)
myosin z-positions over time
myosin x-y positions projected over all simulation time
super-resolution data can help for fitting diffusion coefficient (Mund et al. 2018)
found a new quirk in the model: myosin appears to be displaced upon binding actin (diffusion rate of myosin [light blue dots] is 0 in this example)
- this can also be seen in the x-y plots above
- more detailed collaborative notes here
next steps
- troubleshoot actin-bound myosin movement in simulations
- run a simulation where every single simulation step is output
- validate force-insensitivity of myosin step size
- validate forces exerted on myosin-actin bonds are within reasonable range
- validate forces exerted on myosin-membrane bonds are within reasonable range
- adjust parameters for baseline simulation
- set up new simulation parameters sweeps once baseline model is finished
- develop analysis strategy for characterizing differences in actin organization and how that might explain differences in CME success due to myosin properties